Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus

Journal of Biomedical Science

Morales-Villagrán Alberto²  Santerre Anne¹  Flores-Ponce Xóchitl²  Medina-Ceja Laura² 

[1] Laboratory of Molecular Biomarkers and Molecular Genetic, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Jalisco, Mexico;Laboratory of Neurophysiology and Neurochemistry, Department of Cellular and Molecular Biology, CUCBA,University of Guadalajara, Camino Ing. R. Padilla Sánchez 2100, Las Agujas, Nextipac, Zapopan, Jalisco, Mexico

关键词: Seizures;    Hippocampus;    EEG;    Connexins;    4-Aminopyridine;   

Others  :  1225523
DOI  :  10.1186/s12929-015-0176-5

 received in 2015-03-28, accepted in 2015-08-04,  发布年份 2015

【 摘 要 】

Background

In epilepsy, seizures are generated by abnormal synchronous activity in neurons. In the rat hippocampus (HIP), epileptiform activity has been found to be associated with gap junctions (GJs). GJs are formed by the combination of two hemichannels, each composed of six connexins. At low doses, the convulsive drug 4-aminopyridine (4-AP) produces epileptiform activity without affecting glutamate levels; therefore, GJs could participate in its effect. Based on this argument, in this study, the expression of Cx 32, Cx 36 and Cx 43 protein and mRNA in the HIP of rats treated with 4-AP was evaluated. The evaluation of connexins was carried out by chemifluorescent immunoassay, semiquantitative RT-PCR and immunofluorescence to detect the amount and distribution of connexins and of cellular markers in the HIP and dentate gyrus (DG) of animals treated with NaCl and 4-AP in the right entorhinal cortex. In these animals, convulsive behavior and EEG signals were analyzed.

Results

The animals treated with 4-AP showed convulsive behavior and epileptiform activity 60 min after the administration. A significant increase in the protein expression of Cx 32, Cx 36 and Cx 43 was found in the HIP contralateral and ipsilateral to the site of 4-AP administration. A trend toward an increase in the mRNA of Cx 32 and Cx 43 was also found. An increase in the cellular density of Cx 32 and Cx 43 was found in the right HIP and DG, and an increase in the cellular density of oligodendrocytes in the DG and a decrease in the number of cells marked with NeuN were observed in the left HIP.

Conclusions

Cx 32 and Cx 43 associated with oligodendrocytes and astrocytes had an important role in the first stages of seizures induced by 4-AP, whereas Cx36 localized to neurons could be associated with later stages. Additionally, these results contribute to our understanding of the role of connexins in acute seizures and allow us to direct our efforts to other new anticonvulsant strategies for seizure treatment.

【 授权许可】

   
2015 Laura et al.

【 图 表 】

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